Synthetic rat V1a vasopressin receptor fragments interfere with vasopressin binding via specific interaction with the receptor

Details

Serval ID
serval:BIB_11231FC14EEB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Synthetic rat V1a vasopressin receptor fragments interfere with vasopressin binding via specific interaction with the receptor
Journal
Journal of Biological Chemistry
Author(s)
Mendre  C., Dufour  M. N., Le  R. S., Seyer  R., Guillou  L., Calas  B., Guillon  G.
ISSN
0021-9258 (Print)
Publication state
Published
Issued date
1997
Volume
272
Number
34
Pages
21027-21036
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't
Abstract
To study the vasopressin receptor domains involved in the hormonal binding, we synthesized natural and modified fragments of V1a vasopressin receptor and tested their abilities to affect hormone-receptor interactions. Natural fragments mimicking the external loops one, two, and three were able to inhibit specific vasopressin binding to V1a receptor. In contrast, the natural N-terminal part of the V1a vasopressin receptor was found inactive. One fragment, derived from the external second loop and containing an additional C-terminal cysteine amide, was able to fully inhibit the specific binding of both labeled vasopressin agonist and antagonist to rat liver V1a vasopressin receptor and the vasopressin-sensitive phospholipase C of WRK1 cells. The peptide-mediated inhibition involved specific interactions between the V1a receptor and synthetic V1a vasopressin receptor fragment since 1) it was dependent upon the vasopressin receptor subtype tested (Ki(app) for the peptide: 3.7, 14.6, and 64.5 microM for displacing [3H]vasopressin from rat V1a, V1b, and V2 receptors, respectively; 2) it was specific and did not affect sarcosin 1-angiotensin II binding to rat liver membranes; 3) it was not mimicked by vasopressin receptor unrelated peptides exhibiting putative detergent properties; and 4) no direct interaction between [3H]vasopressin and synthetic peptide linked to an affinity chromatography column could be observed. Such an inhibition affected both the maximal binding capacity of the V1a vasopressin receptor and its affinity for the labeled hormone, depending upon the dose of synthetic peptide used and was partially irreversible. Structure-activity studies using a serie of synthetic fragments revealed the importance of their size and cysteinyl composition. These data indicate that some peptides mimicking extracellular loops of the V1a vasopressin receptor may interact with the vasopressin receptor itself and modify its coupling with phospholipase C
Keywords
1-Sarcosine-8-Isoleucine Angiotensin II/metabolism/Amino Acid Sequence/Animals/Arginine Vasopressin/Binding Sites/Binding,Competitive/Cell Membrane/Cysteine/chemistry/Female/Inositol Phosphates/Kinetics/Liver/Molecular Sequence Data/Peptide Fragments/Phospholipase C/Rats/Rats,Wistar/Receptors,Vasopressin/Tumor Cells,Cultured
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2008 18:35
Last modification date
20/08/2019 12:38
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